Decrease and Senescence of Endothelial Progenitor Cells in Patients With Preeclampsia

Abstract

Both a decrease in endovascular trophoblastic invasion and impaired vascular remodeling of spiral arteries have been cited as possible pathogenetic factors in preeclampsia. The resultant reduction in uteroplacental perfusion consequent to shallow implantation could lead to an hypoxic placenta that releases cytokines and reactive oxygen species, initiating vascular and endothelial dysfunction. Endothelial progenitor cells (EPCs) have been identified in the maternal circulation and, once recruited and mobilized from the bone marrow, are able to restore an intact endothelial lining. There are reports of fewer and less functional EPCs in patients having other disorders, including cardiovascular disease and diabetes. The investigators counted circulating EPCs and assessed their senescence in 8 women with preeclampsia, defined as the development of a blood pressure of 140/90 mm Hg or higher and proteinuria exceeding 300 mg/24 hour after 20 weeks gestation. EPCs were counted by the colony-forming unit (CFU) method, and cellular senescence was estimated by measuring endogenous β-galactosidase activity. In addition, serum levels of the inflammatory marker C-reactive protein (CRP) were determined. EPCs were identified as spindle-shaped cells sprouting from colonies of cultured peripheral blood mononuclear cells. Preeclamptic women, compared with normal control women, had decreased numbers of circulating EPCs (median, 10 vs 34 CFU, P < .01). In addition, the rate of cellular senescence was significantly enhanced in the preeclamptic group (33.9% vs 22.9%). EPC CFU counts were markedly decreased in women whose serum CRP levels were 0.l mg/dL or higher than in CRP-negative patients (5 vs 25 CFU). Median values for cellular senescence were greater in the CRP-positive group but not to a significant degree. These findings clearly point to reduced numbers of EPCs in preeclamptic women and indicate that those cells that are present tend to be more senescent than those without this disorder. These abnormalities are associated with elevated circulating levels of CRP, a marker of systemic inflammation.